Meropenem

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT MEROPEM (MEROPENEM)

Composition:

active substance: meropenem;

1 vial contains meropenem trihydrate equivalent to 0.5 g or 1 g of anhydrous meropenem;

excipient: sodium carbonate anhydrous.

Pharmaceutical form. Powder for solution for injection.

Main physicochemical properties: white crystalline powder or slightly yellowish in color.

Pharmacotherapeutic group. Antimicrobial agents for systemic use. Carbapenems. ATC code J01D H02.

Pharmacological properties.

Pharmacodynamics.

Meropenem exerts a bactericidal effect by inhibiting the synthesis of bacterial cell walls in Gram-positive and Gram-negative bacteria through binding to penicillin-binding proteins (PBP).

As with other beta-lactam antibacterial agents, the duration of time during which meropenem concentrations exceed the minimum inhibitory concentrations (MIC) (T>MIC) correlates highly with efficacy. In preclinical models, meropenem demonstrated activity at plasma concentrations exceeding the MIC for the infecting microorganisms for approximately 40% of the dosing interval. This target value has not been clinically established.

Bacterial resistance to meropenem may arise due to: reduced permeability of the outer membrane in Gram-negative bacteria (due to decreased production of porins); reduced affinity for target PBPs; increased expression of efflux pump components; or production of beta-lactamases capable of hydrolyzing carbapenems. Cases of infections caused by bacteria resistant to carbapenems have been reported.

Cross-resistance between meropenem and medicinal products belonging to the classes of quinolones, aminoglycosides, macrolides, and tetracyclines, with respect to target microorganisms, is absent. However, bacteria may exhibit resistance to more than one class of antibacterial agents when the underlying mechanism involves reduced membrane permeability and/or presence of efflux pump(s).

MIC breakpoint values established during clinical studies by the European Committee on Antimicrobial Susceptibility Testing (EUCAST)

Microorganism	Susceptible (S), (mg/l)	Resistant (R), (mg/l)
Enterobacteriaceae	≤2	>8
Pseudomonas	≤2	>8
Acinetobacter	≤2	>8
Streptococcus, groups A, B, C, G	Note 6	Note 6
Streptococcus pneumoniae1	≤2	>2
Other streptococci2	≤2	>2
Enterococcus species
Staphylococcus species2	Note 3	Note 3
Haemophilus influenzae1 and Mo­ra­xel­la catarrhalis	≤2	>2
Neisseria meningitidis2,4	≤0.25	>0.25
Gram-positive anaerobes, except Clostridium difficile	≤2	>8
Gram-negative anaerobes	≤2	>8
Listeria monocytogenes	≤0.25	>0.25
Breakpoints not related to microbial species5	≤2	>8

1 The susceptibility breakpoints for meropenem against Streptococcus pneumoniae and Haemophilus influenzae in meningitis are 0.25 mg/L (susceptible) and 1 mg/L (resistant).

2 Microbial isolates with MIC values exceeding the S/I breakpoint are very rare or have not been reported to date. Testing for identification and antimicrobial susceptibility for any such isolate should be repeated, and if confirmed, the isolate should be referred to a reference laboratory. Pending clinical outcome data for verified isolates with MICs above the current resistance breakpoints, such isolates should be reported as resistant.

3 Staphylococcal susceptibility to carbapenems is predicted based on susceptibility to cefoxitin.

4 The meropenem breakpoints for Neisseria meningitidis apply only to meningitis.

5 Non-species-specific breakpoints were established primarily based on pharmacokinetic and pharmacodynamic data and do not depend on the MIC distribution of individual species. These breakpoints are intended for use with species not listed in the table and footnotes. The non-species-specific breakpoints are based on the following dosing regimens: EUCAST breakpoints apply to meropenem administered intravenously at 1000 mg three times daily over 30 minutes as the lowest dose. Doses of 2 g three times daily were considered for severe infections and for intermediate/resistant breakpoints.

6 Beta-lactam susceptibility of Streptococcus groups A, B, C, and G is predicted based on penicillin susceptibility.

«–» Susceptibility testing is not recommended, as the organism is a poor target for treatment with this medicinal product. Isolates may be designated as resistant without prior testing.

The prevalence of acquired resistance may vary geographically and over time for individual species; therefore, local information on microbial resistance is desirable, especially when treating severe infections. When necessary, if the local prevalence of resistance is such that the benefit of using the medicinal product, at least for certain types of infections, is questionable, expert consultation should be sought.

The pathogenic microorganisms listed below are identified based on clinical experience and therapeutic treatment guidelines.

Typically susceptible microbial species

Gram-positive aerobes: Enterococcus faecalis⁷, Staphylococcus aureus (methicillin-susceptible)⁸, Staphylococcus species (methicillin-susceptible), including Staphylococcus epidermidis, Streptococcus agalactiae (group B), Streptococcus milleri group (S. anginosus, S. constellatus, and S. intermedius), Streptococcus pneumoniae, Streptococcus pyogenes (group A).

Gram-negative aerobes: Citrobacter freundii, Citrobacter koseri, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii, Neisseria meningitidis, Proteus mirabilis, Proteus vulgaris, Serratia marcescens.

Gram-positive anaerobes: Clostridium perfringens, Peptoniphilus asaccharolyticus, Peptostreptococcus species (including P. micros, P. anaerobius, P. magnus).

Gram-negative anaerobes: Bacteroides caccae, Bacteroides fragilis group, Prevotella bivia, Prevotella disiens.

Species for which acquired resistance may be a problem

Gram-positive aerobes: Enterococcus faecium^7,9.

Gram-negative aerobes: Acinetobacter species, Burkholderia cepacia, Pseudomonas aeruginosa.

Inherently resistant microorganisms

Gram-negative aerobes: Stenotrophomonas maltophilia, Legionella species.

Other microorganisms: Chlamydophila pneumoniae, Chlamydophila psittaci, Coxiella burnetii, Mycoplasma pneumoniae.

7 Species exhibiting intrinsic intermediate susceptibility.

8 All methicillin-resistant staphylococci are resistant to meropenem.

9 Resistance rate >50% in one or more EU countries.

Pharmacokinetics.

In healthy volunteers, the mean plasma elimination half-life is approximately 1 hour; the mean volume of distribution is approximately 0.25 L/kg (11–27 L); the mean clearance is 287 mL/min after a 250 mg dose, decreasing to 205 mL/min after a 2 g dose. After administration of 500, 1000, and 2000 mg doses infused over 30 minutes, mean C_max values were approximately 23, 49, and 115 µg/mL, respectively; corresponding AUC values were 39.3, 62.3, and 153 µg×h/mL. After 5-minute infusions, C_max values were 52 and 112 µg/mL for 500 and 1000 mg doses, respectively. With multiple dosing every 8 hours in patients with normal renal function, accumulation of meropenem was not observed.

In a study involving 12 patients who received meropenem 1000 mg every 8 hours after surgery for intra-abdominal infections, C_max and elimination half-life values were similar to those in healthy volunteers, but the volume of distribution (27 L) was higher.

Distribution

The mean plasma protein binding of meropenem is approximately 2% and is independent of drug concentration. Following rapid administration (≤5 minutes), meropenem pharmacokinetics are biexponential, but this is less evident after a 30-minute infusion. Meropenem has been shown to penetrate well into various body fluids and tissues, including lungs, bronchial secretions, bile, cerebrospinal fluid, female genital tissues, skin, fascia, muscle, and peritoneal exudates.

Metabolism

Meropenem is metabolized by hydrolysis of the beta-lactam ring, forming a microbiologically inactive metabolite. In vitro, meropenem demonstrates reduced susceptibility to hydrolysis by human dehydropeptidase-I (DHP-I) compared to imipenem, thus eliminating the need for concomitant DHP-I inhibitor administration.

Excretion

Meropenem is primarily excreted unchanged by the kidneys; approximately 70% (50–75%) of the administered dose is excreted unchanged within 12 hours. An additional 28% is excreted as the microbiologically inactive metabolite. Fecal excretion accounts for only about 2% of the dose. Measured renal clearance and probenecid effects indicate that meropenem undergoes both glomerular filtration and tubular secretion.

Renal impairment

Renal dysfunction results in higher plasma AUC values and prolonged elimination half-life of meropenem. AUC increased 2.4-fold in patients with moderate renal impairment (creatinine clearance [CrCl] 33–74 mL/min), 5-fold in patients with severe renal impairment (CrCl 4–23 mL/min), and 10-fold in patients on hemodialysis (CrCl <2 mL/min), compared to healthy volunteers (CrCl >80 mL/min). AUC values of the microbiologically inactive open-ring metabolite were also significantly increased in patients with renal impairment.

Dosage adjustment is recommended for patients with moderate and severe renal impairment (see section «Dosage and administration»).

Meropenem is removed by hemodialysis, with a clearance during dialysis approximately 4 times higher than in anuric patients.

Hepatic impairment

Studies in patients with alcoholic liver cirrhosis showed no influence of liver disease on meropenem pharmacokinetics after repeated dosing.

Adult patients

Pharmacokinetic studies in patients revealed no significant pharmacokinetic differences compared to healthy volunteers with similar renal function. A population model developed from data in 79 patients with intra-abdominal infection or pneumonia showed dependence of key parameters on body weight, creatinine clearance, and patient age.

Children

C_max values in infants and children with infection receiving doses of 10, 20, and 40 mg/kg approach those observed in adults after 500, 1000, and 2000 mg doses, respectively. Pharmacokinetic characteristics, including dose-dependent elimination half-lives, were similar to those observed in adults, except in the youngest patients (<6 months – t_1/2 = 1.6 hours). Mean meropenem clearance values were 5.8 mL/min/kg (6–12 years), 6.2 mL/min/kg (2–5 years), 5.3 mL/min/kg (6–23 months), and 4.3 mL/min/kg (2–5 months). Approximately 60% of the dose is excreted in urine within 12 hours as meropenem and an additional 12% as metabolite. Meropenem concentrations in cerebrospinal fluid in children with meningitis are approximately 20% of simultaneous plasma concentrations, although considerable individual variability exists.

Pharmacokinetics of meropenem in neonates receiving antibacterial treatment demonstrated high clearance in neonates with higher chronological or gestational age, with a mean elimination half-life of 2.9 hours.

Elderly patients

Pharmacokinetic studies in elderly healthy volunteers (65–80 years) showed reduced plasma clearance, correlating with age-related reduction in creatinine clearance, and a slight decrease in non-renal clearance. Dosage adjustment is not required for elderly patients, except in cases of moderate to severe renal impairment.

Clinical characteristics.

Indications.

Meropenem is indicated for the treatment of the following infections in adults and children aged 3 months and older:

• pneumonia, including community-acquired and hospital-acquired pneumonia;
• bronchopulmonary infections in cystic fibrosis;
• complicated urinary tract infections;
• complicated intra-abdominal infections;
• infections during childbirth and postpartum infections;
• complicated skin and soft tissue infections;
• acute bacterial meningitis.

Meropenem may be used for the treatment of patients with neutropenia and fever suspected of bacterial infection.

Consideration should be given to obtaining official guidance on the appropriate use of antibacterial agents.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients of the medicinal product.

Hypersensitivity to any other antibacterial agent of the carbapenem group.

Severe hypersensitivity (e.g., anaphylactic reactions, severe skin reactions) to any other type of beta-lactam antibacterial agents (e.g., penicillins or cephalosporins).

Interaction with other medicinal products and other forms of interaction.

Studies on interactions with individual medicinal products, except probenecid, have not been conducted.

Probenecid competes with meropenem for active tubular secretion and thereby inhibits renal excretion of meropenem, resulting in prolonged elimination half-life and increased plasma concentrations of meropenem. Caution should be exercised when probenecid is administered concomitantly with meropenem.

The potential effect of meropenem on protein binding or metabolism of other drugs has not been studied. However, since protein binding is minimal, interactions involving this mechanism are not expected.

Decreased serum levels of valproic acid have been reported when co-administered with carbapenems, resulting in a 60–100% reduction in valproic acid levels within approximately two days. Due to the rapid onset of this interaction, concomitant administration of valproic acid/sodium valproate/valpromide and carbapenems is considered non-adjustable; therefore, such combination should be avoided (see section "Special precautions for use").

Concomitant use of antibiotics with warfarin may enhance its anticoagulant effect. Numerous reports have documented increased anticoagulant effect of oral anticoagulants, including warfarin, in patients receiving antibacterial agents concomitantly. The risk depends on the type of underlying infection, age, and general condition of the patient, making it difficult to assess the exact contribution of antibacterial agents to increased INR (International Normalized Ratio). Frequent monitoring of INR is recommended during and shortly after concomitant use of antibiotics with oral anticoagulants.

Children.

All drug interaction studies have been conducted in adults only.

Special precautions for use

When selecting meropenem as a treatment option, consideration should be given to the appropriateness of using a carbapenem-class antibacterial agent, taking into account factors such as the severity of infection, prevalence of resistance to other suitable antibacterial agents, and the risk of selecting for carbapenem-resistant bacteria.

Resistance in Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter

In the European Union, resistance to penems among Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter varies. When prescribing the drug, local resistance patterns of these bacteria to penems should be taken into account.

Hypersensitivity reactions

Serious, and sometimes fatal, hypersensitivity reactions have been reported, as with other beta-lactam antibiotics (see sections "Contraindications" and "Side effects").

Patients with a history of hypersensitivity to carbapenems, penicillins, or other beta-lactam antibiotics may also exhibit hypersensitivity to meropenem. A careful patient history regarding previous hypersensitivity reactions to beta-lactam antibiotics should be obtained prior to initiating meropenem therapy.

If a severe allergic reaction occurs, administration of the drug must be discontinued immediately and appropriate measures should be initiated.

Severe skin reactions have been reported in patients receiving meropenem, including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), erythema multiforme, and acute generalized exanthematous pustulosis. If signs or symptoms suggestive of these reactions occur, meropenem should be discontinued immediately and alternative therapy considered.

Antibiotic-associated colitis

Cases of colitis associated with antibiotic use, including pseudomembranous colitis, have been reported with nearly all antibacterial agents, including meropenem, with severity ranging from mild to life-threatening. It is therefore important to consider this diagnosis in patients who develop diarrhea during or after meropenem therapy (see section "Side effects"). Consideration should be given to discontinuing meropenem and initiating specific therapy directed against Clostridium difficile. Medicinal products that inhibit intestinal motility should not be prescribed.

Seizures

Seizures have been rarely reported during treatment with carbapenems, including meropenem (see section "Side effects").

Liver function monitoring

Due to the risk of hepatotoxicity (liver function abnormalities with cholestasis and cytolysis) during meropenem therapy, liver function should be closely monitored (see section "Side effects").

Use in patients with hepatic disease: Liver function should be closely monitored in patients with pre-existing liver disease receiving meropenem. Dose adjustment is not required (see section "Dosage and administration").

Meropenem therapy may result in a positive direct or indirect Coombs test.

Concomitant administration of meropenem and valproic acid/sodium valproate/valpromide is not recommended.

Meropenem contains approximately 2 mEq or 4 mEq of sodium per 500 mg or 1 g dose, respectively. This should be taken into account when prescribing the drug to patients on a sodium-restricted diet.

Use during pregnancy or breastfeeding

Data on the use of meropenem in pregnant women are lacking or limited in quantity.

Animal studies have not shown direct or indirect effects on reproductive toxicity. As a precautionary measure, it is advisable to avoid the use of meropenem during pregnancy.

It is unknown whether meropenem is excreted in human breast milk. Meropenem has been detected in very low concentrations in the milk of animals. Considering the benefit of therapy for the mother, a decision should be made whether to discontinue breastfeeding or to discontinue meropenem therapy.

Ability to affect reaction speed when driving or operating machinery

Studies on the effect of the drug on the ability to drive or operate machinery have not been conducted.

When driving a vehicle or operating machinery, particular caution should be exercised due to the possibility of developing headache, paresthesia, or seizures, which have been reported during meropenem use.

Dosage and Administration.

The tables below provide general recommendations for dosing of the medicinal product.

The dose of meropenem and duration of treatment depend on the type of causative pathogen, severity of the disease, and individual patient sensitivity.

Meropenem administered at a dose of up to 2 g three times daily in adults and children with body weight over 50 kg, and at a dose of up to 40 mg/kg three times daily in children, is particularly suitable for treatment of certain infections caused by less sensitive bacterial species (e.g., Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter) or in cases of very severe infections.

Additional dosage recommendations must be followed when treating patients with renal impairment (see below).

Table 1

Recommended doses for adults and children with body weight over 50 kg

Infection	Single dose administered every 8 hours
Pneumonia, including community-acquired and hospital-acquired	500 mg or 1 g
Respiratory tract infections in cystic fibrosis	2 g
Complicated urinary tract infections	500 mg or 1 g
Complicated intra-abdominal infections	500 mg or 1 g
Infections during childbirth and postpartum infections	500 mg or 1 g
Complicated skin and soft tissue infections	500 mg or 1 g
Acute bacterial meningitis	2 g
Treatment of patients with febrile neutropenia	1 g

Meropenem is usually administered as an intravenous infusion over 15 to 30 minutes.

Additionally, doses of up to 1 g may be given as an intravenous bolus injection over approximately 5 minutes. Safety data regarding intravenous bolus administration of the 2 g dose in adults are limited.

Renal impairment.

Table 2

Recommended doses for adults and children weighing more than 50 kg with creatinine clearance less than 51 ml/min

Creatinine clearance (mL/min)	Single dose (see Table 1)	Frequency
26-50	full single dose	every 12 hours
10-25	half the single dose	every 12 hours
<10	half the single dose	every 24 hours

Data regarding the use of the doses of the drug indicated in Table 2, adjusted to the 2 g dose unit, are limited.

Meropenem is removed by hemodialysis and hemofiltration; therefore, the required dose of the drug should be administered after completion of the hemodialysis procedure.

There are no dosage recommendations for patients undergoing peritoneal dialysis.

Hepatic impairment.

Dose adjustment of the drug is not required in patients with hepatic impairment (see section "Special warnings and precautions for use").

Dosing in elderly patients.

Dose adjustment is not required in elderly patients with normal renal function and creatinine clearance values above 50 mL/min.

Children under 3 months of age.

There are no data on the safety and efficacy of meropenem in children under 3 months of age, and the optimal dosing regimen has not been established. There are limited pharmacokinetic data supporting the use of a meropenem dose of 20 mg/kg every 8 hours (see section "Pharmacokinetics").

Table 3

Recommended doses of the drug in children aged from 3 months to 11 years and with body weight up to 50 kg

Infection	Single dose administered every 8 hours
Pneumonia, including community-acquired and hospital-acquired	10 or 20 mg/kg body weight
Respiratory tract infections in cystic fibrosis	40 mg/kg body weight
Complicated urinary tract infections	10 or 20 mg/kg body weight
Complicated intra-abdominal infections	10 or 20 mg/kg body weight
Complicated skin and soft tissue infections	10 or 20 mg/kg body weight
Acute bacterial meningitis	40 mg/kg body weight
Treatment of patients with febrile neutropenia	20 mg/kg body weight

There is no experience with the use of the drug in children with impaired renal function.

Meropenem should be administered as an intravenous infusion lasting from 15 to 30 minutes. Additionally, doses of meropenem up to 20 mg/kg may be administered as an intravenous bolus injection over approximately 5 minutes. Safety data regarding administration of meropenem at a dose of 40 mg/kg as an intravenous bolus injection in children are limited.

Children with body weight above 50 kg.

The dose should be the same as for adult patients.

Administration of intravenous bolus injection

The solution for bolus injection should be prepared by dissolving the medicinal product in water for injections to obtain a concentration of 50 mg/ml.

Chemical and physical stability of the prepared solution for bolus injection was maintained for 3 hours at room temperature (15–25 °C).

From a microbiological standpoint, if the method of opening/reconstitution/dilution does not exclude the risk of microbial contamination, the medicinal product should be used immediately.

If the medicinal product is not used immediately, the physician is responsible for the duration and storage conditions after preparation.

Administration of intravenous infusion

The infusion solution should be prepared by dissolving the medicinal product in 0.9% sodium chloride solution for infusion or in 5% glucose (dextrose) solution for infusion to obtain a concentration of 1–20 mg/ml.

Chemical and physical stability of the prepared infusion solution using 0.9% sodium chloride solution was maintained for 6 hours at room temperature (15–25 °C) or for 24 hours at 2–8 °C. The prepared solution, if refrigerated, should be used within 2 hours after removal from the refrigerator. From a microbiological standpoint, the medicinal product should be used immediately. If the medicinal product is not used immediately, the physician is responsible for the duration and storage conditions after preparation.

The prepared meropenem solution using 5% glucose (dextrose) solution should be used immediately, i.e., within 1 hour after preparation.

It is recommended to use freshly prepared meropenem solutions for intravenous injections and infusions.

Table 4

Solvent	Stability duration (hours) at temperature up to
	25 °C	4 °C
Solutions (1-20 mg/mL), prepared with:
0.9% sodium chloride	8	48
5% glucose	3	14
5% glucose and 0.225% sodium chloride	3	14
5% glucose and 0.9% sodium chloride	3	14
5% glucose and 0.15% potassium chloride	3	14
2.5% or 10% mannitol solution for intravenous infusion	3	14
10% glucose	2	8
5% glucose and 0.02% sodium bicarbonate for intravenous infusions	2	8

When preparing the solution, standard aseptic techniques should be used.

The prepared solution should be shaken before administration.

All vials are intended for single use only.

Do not freeze prepared solutions.

Children.

The drug can be used in children aged 3 months and older.

Overdose.

Relative overdose is possible in patients with impaired renal function if the dose of the drug is not adjusted. Adverse reactions following overdose correspond to the profile of the specified side effects; they are usually mild and resolve after discontinuation of the drug or dose reduction. Symptomatic treatment should be considered as necessary.

In individuals with normal renal function, the drug is rapidly eliminated via the kidneys.

Hemodialysis removes meropenem and its metabolites from the body.

Adverse reactions

During the review of data from 4872 out of 5026 patients regarding the effects of meropenem treatment, the most common adverse reactions associated with the use of meropenem were diarrhea (2.3%), rash (1.4%), nausea/vomiting (1.4%), and injection site inflammation (1.1%). The most common laboratory-related adverse reactions were thrombocytosis (1.6%) and elevated liver enzyme levels (1.5–4.3%).

In the table below, all adverse reactions are listed by system organ class and frequency: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10,000 to < 1/1000); very rare (< 1/10,000); frequency not known (cannot be estimated based on available data).

Within each category, adverse reactions are listed in descending order of severity.

Table 5

System organ class	Frequency	Adverse reaction
Infections and infestations	uncommon	oral and vaginal candidiasis
Blood and lymphatic system disorders	common uncommon frequency unknown	thrombocytosis; eosinophilia, thrombocytopenia, leukopenia, neutropenia; agranulocytosis, hemolytic anemia
Immune system disorders	frequency unknown	angioedema, anaphylactic reactions
Nervous system disorders	common uncommon rare	headache; paraesthesia; convulsions
Gastrointestinal disorders	common uncommon	diarrhea, nausea, vomiting, abdominal pain; colitis associated with antibiotic use
Hepatobiliary disorders	common uncommon	increased levels of transaminases, increased alkaline phosphatase levels in blood, increased lactate dehydrogenase levels in blood; increased bilirubin levels in blood
Skin and subcutaneous tissue disorders	common uncommon frequency unknown	rash, pruritus; urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme; drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), acute generalized exanthematous pustulosis
Renal and urinary disorders	uncommon	increased creatinine levels in blood, increased urea levels in blood
General disorders and administration site conditions	common uncommon frequency unknown	inflammation, pain; thrombophlebitis; pain at injection site

There are no data indicating an increased risk of adverse reactions in children based on the limited available information. All reported events corresponded to adverse reactions observed in adult patients.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after a medicinal product is authorized is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions according to applicable legislation.

Shelf life.

3 years.

Storage conditions.

Keep out of reach and sight of children. Store in the original packaging at a temperature not exceeding 25 °C. Do not freeze.

Incompatibilities.

Meropenem should not be mixed or added to other medicinal products.

Meropenem intended for intravenous bolus injection should be reconstituted with sterile water for injections.

Meropenem in vials for intravenous infusion may be directly reconstituted in 0.9% sodium chloride solution or 5% glucose solution for infusion.

Packaging. 0.5 g or 1 g per vial; 1 or 50 vials per carton.

Prescription status.

Prescription only.

Manufacturer.

Private Joint-Stock Company "Lekhym-Kharkiv".

Manufacturing and packaging of bulk product by the manufacturer Shenzhen Haiyue Pharmaceutical Co., Ltd., China.

Manufacturer's address and location of operations.

36 Severina Pototskoho Street, Kharkiv, Kharkiv Oblast, 61115, Ukraine.